Cationic α-Cyclodextrin:Poly(ethylene glycol) Polyrotaxanes for siRNA Delivery

摘要

RNA interference has broad therapeutic potential due to its high specificity and ability to potentially evade drug resistance. Three cationic α-cyclodextrin:poly(ethylene glycol) polyrotaxanes derived from polymer axle different sizes (MW 2000, 3400 and 10000) have been synthesized for delivering siRNA. These polyrotaxanes are able to condense siRNA into positively charged particles that are < 200 nm in diameter, enabling their facile internalization into mammalian cells. The cationic polyrotaxanes display cytotoxicity profiles that are >10²-fold lower than the commercial standard bPEI and gene silencing efficiencies that are comparable to both Lipofectamine 2000 and bPEI. Our findings suggest that the cationic polyrotaxanes display a size-activity relationship, wherein, the higher molecular weight polyrotaxanes (PEG3400 and 10000) are able to condense and deliver siRNA better than the lower molecular weight material (PEG2000).